PRODUCTION OF CYTOKINES AROUND LOOSENED CEMENTED ACETABULAR COMPONENTS - ANALYSIS WITH IMMUNOHISTOCHEMICAL TECHNIQUES AND IN-SITU HYBRIDIZATION

The chronic inflammatory response to wear particles from orthopaedic joint implants is believed to cause osteolysis and to contribute to prosthetic loosening. Previous in vitro experiments have demonstrated that particulate debris from joint implants causes cells in culture to release products that have been implicated in this pathological bone resorption. The purpose of the current study was to investigate the in vivo features of this complex process in patients who had had a total hip replacement. Membranous tissue was obtained from the cement-bone interface of ten polyethylene acetabular components that had been revised for aseptic loosening in ten patients. The immunoperoxidase technique, which involves the use of specific antibodies for each cell type, showed that macrophages were the predominant cellular constituents but also that fibroblasts, many of which were not identified on plain histological study, were present and were actively producing collagen. T lymphocytes were present variably, but they generally composed less than 10 per cent of the cells. Particulate debris (polyethylene, methylmethacrylate, and metal) was present in all membrane specimens but was intracellular only in macrophages and multi-nucleated giant cells. S-35-labeled nucleic-acid probes, complementary to human interleukin-1-beta and to platelet-derived growth-factor-2 messenger RNA (mRNA), were hybridized with serial tissue sections. Hybridization demonstrated interleukin-1-beta mRNA predominantly in macrophages, and not in fibroblasts or in T lymphocytes to any major extent. In contrast, immunolocalization demonstrated interleukin-1-beta protein on both macrophages and fibroblasts, suggesting that macrophages release interleukin-1-beta, which then binds to both fibroblasts and macrophages. Platelet-derived growth-factor transcripts were found in both macrophages and fibroblasts. CLINICAL RELEVANCE: These data demonstrate that interleukin-1-beta and platelet-derived growth factor, two potent cytokines that have been implicated in many disease states, are produced at the cement-bone interface of failed joint prostheses. These cytokines are probably involved in bone resorption, fibrous proliferation, and, ultimately, loosening of prostheses. Even with technological advances, it is unlikely that particulate wear debris from total joint replacements will be eliminated. However, an understanding of which cytokines cause bone resorption and which cells produce the cytokines will enhance the ability to block the deleterious effects of particulate wear debris and will lead to an increase in the longevity of reconstructed joints.